1. Field of the Invention
The present invention relates to a method for producing N-[N-[3-(3-methoxy-4-hydroxyphenyl)propyl]-L-α-aspartyl]-L-phenylalanine 1-methyl ester from Aspartame, which compound is useful as a sweetener, to a method for purifying the prepared derivative, in particular, to a method for crystallizing N-[N-[3-(3-methoxy-4-hydroxyphenyl)propyl]-L-α-aspartyl]-L-phenylalanine 1-methyl ester, to crystals of derivative which are obtained or can be obtained in these methods, to a sweetener and to other products containing the crystals of the derivative, and the like.
2. Description of the Background
In recent years, eating habits of many have improved to a high level. In this regard, the obesity of individuals which results from excessive sugar intake and the diseases which result from obesity are important health issues. Accordingly, the development of low-calory sweetener (sweetening agent), which replaces sugar, has been in demand. A sweetener that is widely used presently Aspartame. This substance has a high level of safety and an excellent quality of sweetness. However, Aspartame presents problems of stability. International Patent Publication WO94/11391 discloses that compounds (derivatives of Aspartame) in which an alkyl group is introduced onto the amino group of aspartic acid, which constitutes Aspartame have been studied as one approach to slightly improve the stability of Aspartame and to improve its sweetening potency. Of the compounds disclosed in this publication, N-[N-(3,3-dimethylbutyl)-L-α-aspartyl]-L-phenylalanine 1-methyl ester exhibits the most excellent sweetening potency. The sweetening potency of this compound is reported to be 10000 times that of sucrose. One method employed for producing this compound is the reductive alkylation of Aspartame with sodium cyanoborohydride in the presence of 3,3-dimethylbutylaldehyde in methanol (see French Patent Publication FR2697844.). Another method of reductive alkylation is the reduction of Aspartame with hydrogen in the presence of 3,3-dimethylbutylaldehyde in the presence of platinum on carbon as a catalyst at a pH of 4.5 to 5.0 in a mixed solvent of water-methanol (see the International Patent Publication WO95/30689.). Still another of reductive alkylation is reduction of Aspartame under 0.2 MPa of hydrogen pressure in the presence of 3,3-dimethylbutylaldehyde in the presence of palladium on carbon catalyst in methanol (see U.S. Pat. No. 5,728,862). However, with regard to other Aspartame derivatives, for example, N-[N-[3-(3-methoxy-4-hydroxyphenyl)propyl]-L-α-aspartyl]-L-phenylalanine 1-methyl ester, where the sweetening potency is reported to be 2500 times that of sucrose, the various physico-chemical data are not disclosed. Moreover, there are no operational examples which should show what is used as a starting material; nor is there any disclosure of how the synthesis is conducted. Other derivatives are also not described concretely. Accordingly, a method for producing practically and industrially the compound, including a method for purifying the same, has not been studied.